In 2005, a total of 65,479 persons died of cancer in Korea, accounting for 26.70 out of total deaths. 28.4 (21.1%) died of lung cancer, which is the leading cause of cancer-related death, 22.6 (16.8%) died of gastric cancer, 22.5 (16.7%) died of liver cancer, and 12.5 (9.3%) died of colon cancer per 100000 population. In spite of the decline in its mortality rate from 24% to 16% for the 10 years from 1996 to 2006, gastric cancer still remains one of the three leading causes of cancer death in Korea (see Table 1).
Mortality rate and Proportion of 10 Major Cancers in2005 (source; National Statistical Office, 2005)
In addition, it is estimated that gastric cancer causes more than 16% of the male deaths in Korea or Japan. It is believed that a high incidence of gastric cancer in Asia including Korea and Japan is not due to race but due to differences in environmental factors which are strongly correlated with the occurrence of cancer, in particular, diet. The daily salt intake is known to be approximately 20 g in Korea, which are 2-fold higher than that in western countries. In particular, the high incidence of gastric cancer is reported in Korea, Japan, Finland, and Iceland, where salted fish is consumed. In addition, hereditary factors, as well as diet, have been suggested as a cause of gastric cancer. It appears that first-generation offspring of gastric cancer patients and people with blood type A are at increased risk of gastric cancer. Helicobacter Pylory (H.p) infection is one of the major risk factors for developing gastric cancer. The relationship between Helicobacter pyloric infection and gastric cancer has not been fully clarified yet, but Helicobacter pyloric infection is observed in 40-60% of Korean patients with digestive tract disorders or gastric cancer, indicating that individuals infected with H. pylori are at high risk of developing gastric cancer, compared with non-infected individuals. Therefore, eradication of H. pylory has been proposed for the prevention of gastritis and gastric cancer.
The underlying mechanism of cancer development remains poorly defined, but it is generally understood that cancer is the result of genetic events that disrupt the normal regulation of cell proliferation. Early gastric cancer is defined as tumor invasion confined to the mucosa, which has a considerably better prognosis. Thus, early diagnosis and treatment of gastric cancer contribute to the reduction of the mortality rate and cancer treatment cost.
Gastric cancer may exhibit with a wide range of symptoms from no symptoms to severe pain, and the symptoms are not marked characteristic symptoms, but overlap with the symptoms of various digestive illnesses. At an early stage, gastric cancer rarely causes symptoms, which if present, resemble typical digestive disorder or abdominal discomfort. Thus, people often ignore these symptoms, leading to an increase in the mortality rate.
To date, the diagnosis of gastric cancer has been made by physical examination. First, gastrointestinal X-ray examination methods may be broadly classified into the double contrast method, the compression method, the mucosal relief method, etc. Second, endoscopic examination is advantageous in that it directly visualizes the mucosa to find small lesions that are not detected by X-ray, and permits biopsy of suspicious lesions, whereby the diagnosis rate is increased. However, endoscopic examination has problems that there is a chance of contamination, and patients have to experience significant discomfort during the procedure.
In addition, surgical resection of the lesion is the most effective treatment for gastric cancer, and is the only curative treatment currently available for gastric cancer. Various methods can be employed in the surgical resection. For complete cure, surgical resection with a maximum surgical margin is generally recommended, but the extent of surgery may be determined in consideration of postoperative complications. At this time, other organs including nearby lymph nodes as well as the stomach are included in the surgical resection, and the extensive surgery may create a poor prognosis. Further, when gastric cancer spreads to other organs, radical surgery is not possible, and thus chemotherapy is adopted. Anticancer agents currently available serve to temporarily alleviate symptoms or to prevent recurrence and prolong survival time after surgical resection. However, chemotherapy causes severe side effects, and also imposes economic burden on the patients.
For the development of diagnostic agents for detecting the occurrence and development of gastric cancer and therapeutic agents as alternatives to solve the problems of surgical resection or chemotherapy, it is a prerequisite and an object of the present invention to screen biomarkers and to develop agents measuring the level of diagnostic marker.
On the other hand, human tumors express and secrete various specific molecules called cancer marker antigens. Currently, the sera of cancer patients are analyzed, and a variety of antigens have been provided for the diagnosis and treatment of cancer development and metastasis. As many as 60 tumor markers have been discovered thus far. Among them, some cancer markers are commercially applied, including AFP (hepatic cancer), CEA (colon, gastric, pancreatic, breast cancers), HCG (choriocarcinoma), PAP (prostate cancer), NSE (lung cancer), C15-3 (breast cancer), and CA19-9 (colon cancer, pancreatic cancer). Diagnostic markers or therapeutic agents which are highly useful in the diagnosis and treatment of gastric cancer, however, have not yet been developed.